Gastroesophageal Case

A 76-Year-Old Woman with JOHN MULLEN, MD Massachusetts General Hospital

PRESENTATION OF CASE . Staging computed tomography (CT) scans of the chest, abdomen and pelvis A 76-year-old woman was seen in our only showed prominent lymph nodes adjacent multidisciplinary gastrointestinal clinic to the lesser curvature of the stomach within for further management of an adenocarcinoma of the gastrohepatic ligament and no evidence of the body of the stomach. metastatic disease. The patient presented to her primary care Upon evaluation at our cancer center, she reported physician with a four-week history of intermittent intermittent upper abdominal discomfort that chest pressure radiating to her back. Extensive was worse without food but was typically relieved evaluation for a cardiac source was unremarkable, with eating. She denied any change in appetite or including a normal stress test and abdominal weight. She had no , , early satiety ultrasound. She then developed epigastric or change in her bowel habits. , and given that she carried a history of prior H. pylori infection in 2003, Her past medical history was notable for type there was concern that she might have a peptic II mellitus, hypertension, elevated ulcer. An upper was obtained and lipids, gastroesophageal reflux disease (GERD), showed a large ulcerated tumor in the body of diverticulosis, endometriosis, kidney stones, the stomach (Figure 1). Pathological examination anxiety and osteopenia. Her medications included of specimens of the stomach ulcer atorvastatin, Inderal, lisinopril, metformin, showed moderately to poorly differentiated and Paxil. She had allergies to dyazide, morphine, intravenous contrast dye, and triamcinolone cream. She was a retired research assistant and was married with two children. She never smoked and did not drink alcohol. There was no family history of , but her older brother died of colon cancer metastatic to the and at the age of 90. On examination, the weight was 182 pounds, the blood pressure 182/90 mm Hg, the pulse 90 beats per minute and the temperature 97.2 degrees Fahrenheit. There was mild epigastric tenderness

FIGURE 1. Image from upper endoscopic examination without a palpable mass nor an enlarged liver. demonstrating a large ulcerated tumor in the body Results of a complete blood count, plasma levels of the stomach.

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of electrolytes and tests of kidney and liver Given this patient’s advanced age and function were normal. medical co-morbidities, it was decided by the multidisciplinary team of surgical oncology, DISCUSSION OF MANAGEMENT medical oncology and radiation oncology that the safest approach would be upfront surgery followed This patient has a stomach cancer that appears by postoperative and radiation to be locoregionally advanced on imaging studies. therapy. The patient was felt to be at high risk for The first decision regarding management is complications from either ECF chemotherapy whether to resect it immediately or to administer or even a milder regimen of 5-FU, leucovorin preoperative chemotherapy, with or without and (FOLFOX) chemotherapy, and preoperative . we did not want to preclude the most important Treatment of Locoregionally Advanced component of her treatment for potential cure – Gastric Cancer that being a .

Although surgery is the mainstay of curative Accordingly, the patient was cleared for surgery treatment for gastric cancer, even after complete by her cardiologist and primary care physician resection, more than half of patients with and was taken to the operating room for a locally advanced tumors recur, and fewer than subtotal gastrectomy and D2 . 40% survive beyond three years1. Accordingly, Since gastric cancer frequently spreads to the investigators around the world have explored a regional lymph nodes, and since at least 16 lymph variety of adjuvant and neoadjuvant multimodality nodes should be removed and examined by the treatment approaches to this disease. In North pathologist for the most accurate staging of gastric America, the standard approach has long cancer1, we routinely remove not only the lymph been upfront surgery followed by adjuvant nodes immediately adjacent to the stomach (the chemoradiotherapy, based on the findings of so-called D1 lymph nodes, in stations 1-6), but the Intergroup 0116 trial, which showed that we also remove the second tier of lymph nodes postoperative 5- (5-FU)/leucovorin- along the major blood vessels to the liver, stomach based chemoradiation increases overall survival in and spleen (the so-called D2 lymph nodes, in comparison to surgery alone.2 However, another standard of care for resectable gastric cancer in North America and Europe emerged with the publication of the MAGIC trial3 a few years later and the FNCLCC/FFCD multicenter phase III trial4 a few years after that. The MAGIC trial reported an improvement in overall survival with perioperative , and 5-FU (ECF) compared to surgery alone, and the FNCLCC/FFCD trial showed an improved R0 resection rate and survival FIGURE 2. stations including (A) the with perioperative 5-FU and cisplatin. perigastric, or D1, lymph nodes (stations 1 to 6), and (B) the regional, or D2 and D3, lymph nodes (stations 7-16).

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stations 7-12) (Figures 2A and 2B)6. In fact, since (tumor penetrates ) and pN2 (3 nodes 2006, we have been performing this technically positive out of 31 nodes examined), or stage IIIA1. demanding “D2 lymphadenectomy” with a low All margins were negative, and there was evidence risk of complications and no deaths, and the of both perineural and lymphovascular invasion. median number of examined lymph nodes was Based on the advanced nature of her cancer 40, and more than 90% of patients had at least 16 and the results of the Intergroup 0116 trial, lymph nodes examined5. In this patient’s particular which showed a survival advantage for adjuvant operation, we removed approximately 80% of the chemoradiation therapy, we treated her with stomach and reconstructed the gastrointestinal eight cycles of FOLFOX chemotherapy followed tract with a Roux-en-Y gastrojejunostomy by five weeks of 5-FU-based chemoradiation (Figure 3)6. This procedure was accomplished therapy to 45 Gray. She tolerated all of this therapy through an open approach via an upper midline remarkably well and remains free of disease abdominal incision and was uncomplicated. Her today. Her chance of long-term survival is on the postoperative course was unremarkable, and she order of 30%, and it is in large part because of the was discharged to home on postoperative day coordinated efforts of our team that specializes number six, eating a soft diet composed of six in gastric cancer that this patient made it through small meals spaced evenly throughout the day. all stages of her treatment and thus has the best possible chance for a cure.

REFERENCES 1. Edge SB, Byrd DR, Compton CC, et al. AJCC manual. 7th ed. New York: Springer-Verlag;2009:117-126. 2. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725-730. 3. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11-20. 4. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715-1721. 5. Schmidt B, Chang KK, Maduekwe UN, et al. D2 FIGURE 3. Reconstruction by a retrocolic, lymphadenectomy with surgical ex vivo dissection into node Roux-en-Y gastrojejunostomy. stations for gastric adenocarcinoma can be performed safely in Western patients and ensures optimal staging. Ann Surg Oncol Pathological Discussion and Role of Adjuvant 2013;20:2991-2999. Chemoradiation Therapy 6. Mullen JT. Subtotal gastrectomy for gastric cancer. In: Fischer JE, Bland KI, Callery MP, Clagett GP, Jones DB, editors. Mastery of Pathological examination showed a 4 cm tumor Surgery. Philadelphia: Lippincott, Williams, and Wilkins; Sixth in the body of the stomach that was moderately edition, 2012. to poorly differentiated and was staged as pT3

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